In this study, we performed a comprehensive analysis of BRCA1/2 variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in BRCA1 and BRCA2. This study included 5433 Korean participants who were tested for BRCA1/2 genes. The BRCA1/2 variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had BRCA1 or BRCA2 PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for BRCA2 VUS than those of BRCA1 VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1–73.6%) for BRCA1 and 58.3% (95% CI: 43.2–73.0%) for BRCA2 carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4–53.9%) for BRCA1 and 14.9% (95% CI: 7.4–28.5%) for BRCA2 carriers.
Bibliographical noteFunding Information:
Funding: This research was conducted with support from AstraZeneca Korea Ltd. This work was also supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2019R1A2C2002177).
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Cancer Research